ORIGINAL ARTICLE

Gated SPECT myocardial perfusion imaging with cadmium-zinc-telluride detectors allows real- time assessment of dobutamine-stress-induced wall motion abnormalities

Rene Nkoulou, MD,a,b Mathias Wolfrum, MD,a Aju P. Pazhenkottil, MD,a Michael Fiechter, MD,a Ronny R. Buechel, MD,a Oliver Gaemperli, MD,a and Philipp A. Kaufmann, MDa

a Department of Nuclear , University Hospital Zurich, Zurich, Switzerland b Department of Cardiology, University Hospital Geneva, Geneva, Switzerland

Received Mar 25, 2017; accepted Dec 18, 2017 doi:10.1007/s12350-018-1187-x

Background. Left ventricular (LV) (EF) during high dobutamine stress (HD) by real-time gated-SPECT myocardial perfusion imaging (MPI) on a cadmium-zinc- telluride (CZT) was validated versus cardiac magnetic resonance imaging (CMR). Methods and results. After injecting 99mTc-tetrofosmin (320 MBq) in 50 patients (mean age 64 1/2 11 years), EF at rest and post-stress as well as relevant changes in EF at HD (DEF ‡ 5%) were assessed. CZT and CMR rest EF values yielded an excellent correlation and agreement (r = 0.96; P < 0.001; Bland–Altman limits of agreement (BA): 1 0 to 14.8%). HD EF acquisition was feasible using CZT and correlated better to HD CMR EF than did post-stress CZT EF (r = 0.85 vs 0.76, respectively, all P < 0.001). Agreement in DEF detection between HD CMR and immediate post-stress CZT (reflecting standard acquisition using conventional SPECT camera unable to scan during stress) was 45%, while this increased to 85% with real- time HD CZT scan. Conclusion. Real-time ultrafast dobutamine gated-SPECT MPI with a CZT device is feasible and provides accurate measurements of HD LV performance. (J Nucl Cardiol 2019;26:1734–42.) Key Words: Cadmium-zinc-telluride detectors gamma camera Æ Dobutamine-stress Æ Wall motion abnormalities

Abbreviations LVWT Left ventricular wall thickening CMR Cardiac magnetic resonance imaging MPI Myocardial perfusion imaging CZT Cadmium-zinc-telluride detectors TID Transient ischemic dilation SPECT single photon emission computed tomography LVWM Left ventricular wall motion

See related editorial, pp. 1743–1745

Electronic supplementary material The online version of this Reprint requests: Rene Nkoulou, MD, Department of Nuclear Medi- article (https://doi.org/10.1007/s12350-018-1187-x) contains sup- cine, University Hospital Zurich, Rðmistrasse 100, 8091 Zurich, plementary material, which is available to authorized users. Switzerland; [email protected] The authors of this article have provided a PowerPoint file, available 1071-3581/$34.00 for download at SpringerLink, which summarises the contents of the Copyright Ó 2018 American Society of Nuclear Cardiology. paper and is free for re-use at meetings and presentations. Search for the article DOI on SpringerLink.com.

1734 Journal of Nuclear CardiologyÒ Nkoulou et al. 1735 Volume 26, Number 5;1734–42 Myocardial perfusion imaging, CZT detector gamma camera, dobutamine

INTRODUCTION study was approved by the local ethics committee and all study participants provided written informed consent. Myocardial perfusion imaging (MPI) using single photon emission computerized tomography (SPECT) is one of the best established imaging modalities for the Stress Protocol non-invasive detection of patients with coronary artery After a rest ECG and obtaining an intravenous line, disease (CAD). This is partly due to the fact that dobutamine was administered intravenously by an infu- perfusion abnormalities, which are the target of SPECT sion pump, starting at a low dose of 10 ug/kg/min (LD) MPI, occur very early in the ischemic cascade.1 Imple- for 5 minutes and then increasing by 10 ug/kg/min every mentation of ECG-gated acquisition has improved the 3 minutes, to achieve 85% of age-predicted maximal accuracy of SPECT as it allows to distinguish between rate (220-age), up to a maximum of 40 ug/kg/min. true fixed defects and attenuation artifacts2 and it Atropine 0.5 to 1 mg iv was added whenever needed to confers an added prognostic value over MPI alone.3 achieve the target heart rate. Throughout the pharmaco- Dynamic changes in global and regional LV contractil- logic stress continuous 12-lead ECG and intermittent ity under stress conditions are a strong predictor of blood pressure monitoring were recorded. Dobutamine adverse events in a wide range of cardiovascular was stopped prior to reaching the target heart rate in case conditions including CAD,4-6 dilated cardiomyopathy,6 of severe hypertensive response (blood pressure [ 220/ and valvular dysfunction.7 120 mm hg), systolic hypotension (\80 mm Hg), blood The current SPECT gamma camera generation pressure drop [ 40 mm Hg compared to baseline, requires an acquisition time for MPI and gated-SPECT significant arrhythmia, horizontal or downsloping ST of 15 minutes or longer. This precludes an assessment of segment depression [ 0.20 mV at an interval of 80 ms LV function and diameter during maximal stress. Thus, from the J point compared to baseline, ST segments the widely used transient ischemic dilation (TID) is elevation [ 0.1 mV in patients without previous based on values assessed after stress, and could therefore myocardial infarction.10 be subject to changes due to early recovery during the relatively long scan period. The latest generation of SPECT cameras with cadmium-zinc-telluride (CZT) SPECT Data Acquisition and Reconstruction detector technology offers ultrafast MPI assessment at All SPECT MPI’s were performed on a hybrid 3 minutes acquisition time8,9 and may therefore be CZT/CT device (DNM 570c, GE Healthcare, Milwau- potentially used for sequential real-time EF acquisition kee). The CZT part is a gamma-camera equipped with by gated-SPECT at each step of a standard dobutamine 19 non-rotating CZT solid state detector modules stress protocol. We thus aimed at evaluating the feasi- positioned around the chest.11-13 This camera enables bility of EF measurements and its accuracy to detect low-dose radiotracer MPI acquisition within 3 minutes clinically relevant changes in EF (DEF) during standard and high-dose radiotracer acquisition within 2 minutes.8 dobutamine stress protocol assessed by real-time high- After a CT scan for attenuation correction,14,15 320 MBq speed gated-SPECT using cardiac magnetic resonance of 99mTc-tetrofosmin were injected, and MPI as well as imaging (CMR) with dobutamine stress as standard of LV function were assessed at rest twice consecutively reference. over 3 minutes each. Thereafter, dobutamine was started and LV function was assessed from gated-MPI (3 MATERIAL AND METHODS minutes acquisitions each) after reaching a steady-state during low-dose dobutamine (LD) (10 ug/kg/min) and at Patient Population peak-stress during maximum dobutamine dose (HD). Immediately after finishing HD image acquisition, 960 Fifty consecutive patients referred for SPECT MPI MBq of 99mTc-tetrofosmin was injected while dobu- were enrolled for the feasibility study (including repro- tamine was continued for 1 more minute and gated post- ducibility and repeatability for the rest scan). Exclusion stress images were acquired 5 min later. Thus, this criteria were any contraindication to dobutamine includ- protocol allows assessing MPI at rest and at HD stress, ing recent unstable angina, uncontrolled hypertension, but also allows LV functional data at rest, at LD and aortic aneurysmal disease, or severe aortic stenosis. An HD, as well as early post-stress. The latter reflects the additional rest/dobutamine-CMR was performed in a traditional setting with a standard SPECT camera which subgroup of 20 within 2 weeks during which no change does not allow real-time LV function assessment in clinical condition including medication or revascu- because acquisition time exceeds by far the short time larization occurred for validation of the precision. The of HD dobutamine tolerable by patients. The widely used TID is based on such post-stress data which may 1736 Nkoulou et al. Journal of Nuclear CardiologyÒ Myocardial perfusion imaging, CZT detector gamma camera, dobutamine September/October 2019 substantially differ from the real value at stress. All Systems, Best, the Netherlands) with prospective ECG- SPECT images were acquired with ECG gating and in triggering. Scout images served to determine 4-chamber, list-mode.9,11 A schematic representation of the scan- 2-chamber, 3-chamber views, and 3 basal to apical ning protocol is displayed in Figure 1. short-axis views of the left ventricle. Volume measure- Reconstruction of gated-SPECT was performed ments were obtained after multiphase gradient-echo using dedicated software (Myovation for Alcyone, GE (repetition time/echo time 30/10 ms, section thickness Healthcare, Milwaukee) including CT-based attenuation 10 mm, flip angle 40-50, matrix of 128 9 128 correction as previously described14 and validated for reconstructed in 256 9 256). Measurements during LD this CZT device15: list-mode files were used to generate and HD were performed after injection of contrast media 2 separate rest MPI gated scans (3 minutes each). All used for rest perfusion evaluation (0.1 mmol of gadolin- scans were rebinned into 8 frames encompassing the ium per kilogram of body weight, Gadovist 1.0; Bayer entire R-R interval with a 10% acceptance window for Schering Pharma, Berlin, Germany). LV volumes were bad-beat rejection. Reconstructed files were analyzed calculated from the gradient-echo MR images using an using the commercially available QGS/QPS software analytical software package (QMass MR, version 7.2; package (Cedars Sinai, California, USA) yielding quan- Medis systems, Leiden, the Nether- titative values for left ventricular (LV) end-diastolic lands). After endocardial delineation, EDV and ESV (EDV) and end-systolic volumes (ESV), and ejection were identified as the frames with maximal and minimal fraction (EF). Regional values of LV wall motion cavity volume. Regional contractility was analyzed (LVWM) and thickening (LVWT) were generated for visually by two experienced readers at rest and during each coronary artery territory, i.e., left anterior descend- dobutamine infusion. ing (LAD), circumflex (CX), and right coronary artery (RCA) according to standardized myocardial segmenta- Statistical Analysis tion models.16 Cardiac output was calculated as the product of volume (EDV minus ESV) times heart Values were expressed as mean (SD) or median rate. The rest studies were assessed for repeatability by a with interquartile range (IQR) where appropriate. Means single observer. Stress ECG and list mode heart rate were compared using a two-tailed paired-t test or Mann– display were reviewed for quality control. Whitney U test, respectively. Correlation between mea- surements was assessed using Pearson’s correlation and systematic biases were illustrated by Bland–Altman CMR Acquisition and Reconstruction limits of agreement.17 The variation between measure- All CMR studies were performed in expiration ments was expressed by the coefficient of variation using a 1.5 Tesla system (Achieva, Philips Medical (COV = 100 * standard error of the mean/ mean of the

Figure 1. Scanning protocol for real-time acquisition of EF during SPECT MPI. CTAC, computed tomography attenuation correction scan; MHR, age-predicted maximal heart rate; LD, low-dose dobutamine; HD, peak-stress at high-dose dobutamine; P dobu, post-stress. Journal of Nuclear CardiologyÒ Nkoulou et al. 1737 Volume 26, Number 5;1734–42 Myocardial perfusion imaging, CZT detector gamma camera, dobutamine

Table 1. Baseline characteristics of the study population

All SPECT MPI SPECT MPI with CMR n 50 20 Male sex, n (%) 37 (74) 15 (75) Age in years, mean (SD) 64 (11) 63 (10) Body mass index in kg/m2, mean (SD) 26.9 (4.9) 26.3 (4.3) Known CAD, n (%) 15 (30) 5 (25) Cardiovascular risk factors, n (%) Hypertension 38 (76) 12 (60) Dyslipidemia 27 (54) 11 (55) Diabetes 8 (16) 6 (30) Smoking 16 (32) 8 (40)

MPI, myocardial perfusion imaging; CAD, coronary artery disease; CMR, cardiac magnetic resonance imaging

Table 2. Global and regional functional parameters during sequential gated-SPECT under dobutamine n = 50, mean (SD) Rest LD HD Post-stress

EF 49 (15) 51 (16) 62 (18)* 56 (17)** EDV 107 (59) 112 (63) 91 (52)* 102 (62)** ESV 60 (63) 62 (50) 42 (49)* 53 (63)** CO 3.06 (0.86) 3.65 (1.18)* 6.45 (1.83)* 4.22 (1.72)** LVWM 6.1 (2.4) 6.3 (2.3) 7.8 (3.2)* 7.1 (2.9)** LVWT 29 (14) 31 (15) 43 (21)* 33 (16)**

LD, low-dose dobutamine; HD, peak-stress at high-dose dobutamine; EF, left ventricular ejection fraction in %; EDV, end diastolic volume in mL; ESV, end systolic volume in mL; CO, cardiac output in L/min; LVWM, left ventricular wall motion in mm; LVWT, left ventricular wall thickening in per vessel territory in% *Denotes significant changes (P \ 0.05) compared to rest **Denotes significant changes compared to HD estimates). Agreement rates between trends of EF during doses. In 1 patient, dobutamine infusion was discontin- SPECT and CMR were provided. A DEF change [ 5% ued early due to chest pain associated with [ 2mmST between rest and peak-stress was considered to denote segment depression and blood pressure drop of 20 mm clinically a significant change. Receiver operator char- Hg. There were no significant differences between the acteristics (ROC) analysis was used to derive optimal subgroup of patients undergoing additional CMR and cut-off points for LVWM and LVWT to discriminate the entire population with regard to baseline coronary territories presenting with at least one dys- characteristics. functional segment on stress CMR. All P values \ 0.05 were considered statistically significant. Repeatability of Volume Assessment by Gated-SPECT RESULTS Table 2 shows mean volumes and functional param- Baseline characteristics of the study population are eters at rest and during dobutamine stimulation. Fifteen summarized in Table 1. All fifty patients completed the patients presented with a rest LVEF lower than 45% by SPECT MPI successfully and without complication. No gated SPECT. The correlation obtained by repeat rest patient presented with atrial fibrillation or significant evaluations was excellent for EF (r = 0.99; P = 0.001), rhythm irregularity. The median examination time of the EDV (r = 0.97; P = 0.001), ESV (r = 0.99; P = 0.001), entire CZT MPI was 48 min (IQR: 42-58 minutes). Of LVWM (r = 0.92; P = 0.001), and LVWT (r = 0.93; P = all 50 patients, 9 (18%) did not reach their target 0.001). These values showed a COV of 4%, 12%, 13%, maximal heart rate despite optimal pharmacologic stress 16%, and 18%, respectively. Correlation and Bland– 1738 Nkoulou et al. Journal of Nuclear CardiologyÒ Myocardial perfusion imaging, CZT detector gamma camera, dobutamine September/October 2019

Correlation with CMR Volume Assessment The parameters of LV function obtained at rest and peak-stress using gated-SPECT and CMR are provided in Table 3. An excellent correlation was found between CMR and gated-SPECT for rest EF (r = 0.96; P = 0.001; BA limits of agreement, ? 0% to ? 14.8%), EDV (r = 0.91; P = 0.001; ? 0to? 86 mL), and ESV (r = 0.96; P = 0.001; - 14 to ? 34 mL) (Figure 3). At peak-stress and post-stress, these correlations for EF, EDV, and ESV were, respectively, of 0.85, 0.70, 0.77 and 0.76, 0.49, 0.69, respectively (all P \ 0.001). At HD, gated- SPECT identified 14 of 16 patients with DEF C 5%, and 3 of 4 with stable or decreasing DEF by stress CMR resulting in an agreement rate of 85% (17/20 patients; kappa= 0.57; 95% CI: 0.14 to 1). Post-stress gated- SPECT allowed identifying 8 of 16 patients with increasing DEF, and 1 of 4 with stable or decreasing DEF by stress CMR with an agreement rate of 45% (9/ 20 patients; kappa = - 0.17; CI - 0.5 to 0.18).

Optimal Cut-Off Value for LVWM and LVWT Visual analysis of regional contractility in coronary territories using CMR at rest (60 territories) and at HD (60 territories) revealed contractile dysfunction in 27/ 120 coronary territories LAD, CX, RCA territories affected on 6, 9, and 12 occasions. Table 4 summarizes the results from ROC analysis and optimal cut-off values of LVWM and LVWT to detect regional wall motion abnormalities on CMR. An illustrative case of the added value of real-time peak-stress over conventional post- stress gated-SPECT acquisition is presented in Figure 4.

SPECT Perfusion Findings Perfusion studies revealed normal/abnormal find- ings in 38/12 patients and 133/17 coronary territories (7 on LAD, 6 on CX, and 4 on RCA territories, respec- tively). LVWM and LVWT abnormalities were associated with perfusion defects in 13 and 11 coronary territories during HD, and in 13 and 14 post-stress. Also, 24 and 22 additional coronary territories with normal perfusion findings showed abnormal LVWM and LVWT, respectively, during HD while 24 and 32 proved abnormal during post-stress study, respectively. How- Figure 2. Correlation (A) and Bland–Altman bias (B) obtained during repeated evaluation of volumes and contractile ever, a disagreement between HD and post-stress parameters. EF, ejection fraction; EDV, end systolic volume; acquisitions concerning LVWM and LVWT abnormal- ESV, end systolic volume; LVWM, left ventricular wall motion; ities was observed in 22/150 (agreement rate: 85%) and LVWT, left ventricular wall thickening; CoV, coefficient of 28/150 (agreement rate: 81%) coronary territories, variation. respectively. In those patients with both CZT MPI and Altman plots of volumes and contractile parameters CMR, the CZT MPI revealed normal/abnormal findings during repeat rest examinations are displayed in in 13/7 patients. Only 1 patient with abnormal perfusion Figure 2. finding by CZT MPI did not denote increased DEF Journal of Nuclear CardiologyÒ Nkoulou et al. 1739 Volume 26, Number 5;1734–42 Myocardial perfusion imaging, CZT detector gamma camera, dobutamine

Table 3. Parameters of left ventricular function at rest, peak-stress, and post-stress using gated-SPECT (CZT) and MRI

Rest HD Post-stress n =20 Mean (SD) CMR CZT r CMR CZT r CZT R’

EF 58 (13) 50 (14) 0.96* 67 (13) 64 (17) 0.85* 61 (17) 0.76* EDV 141 (54) 95 (48) 0.91* 89 (21) 80 (41) 0.70* 88 (51) 0.49* ESV 64 (51) 51 (46) 0.96* 23 (11) 37 (39) 0.77* 41 (49) 0.69*

CZT, myocardial perfusion imaging using ultrafast cadmium-zinc-telluride gamma camera; CMR, cardiac magnetic resonance imaging; HD, peak-stress at high-dose dobutamine; EF, left ventricular ejection fraction in %; EDV, end diastolic volume in mL; ESV, end systolic volume in mL; CO, cardiac output in L/min; HR, heart rate in beats/min; r = Pearson correlation value between CMR and CZT; R’ = Pearson correlation value between CMR HD and CZT post-stress * All P values \ 0.001; n.a: not available

DISCUSSION The findings of the present study demonstrate that, using a novel CZT-equipped ultrafast SPECT camera, real-time peak-stress gated SPECT is feasible with short acquisition times of 3 min allowing accurate measure- ments of LV volumes and function during sustained maximal stress. So far, assessment of TID is based on the comparison of LV volumes at rest versus post-stress, as the current SPECT camera generation does not allow ultrafast scanning in order to evaluate volumes at the Figure 3. Correlation (A) and Bland–Altman graph (B) short peak-stress period. Nevertheless, TID has been between ejection fractions (EF) obtained using SPECT and shown to confer significant added diagnostic and prog- CMR. nosis value.18,19 However, it seems reasonable to assume that TID calculated from volumes during peak-stress change at stress by CMR. A perfect agreement between would be favorable as this may better reflect the CMR and gated SPECT at HD was observed for trends ischemic reaction while the post-stress volumes may in DEF, whereas disagreement was observed in one underestimate this due to recovery. This is supported by patient with increasing DEF by CMR and stable DEF by the fact that there was an excellent agreement between gated SPECT at post-stress. peak-stress LVEF from CZT compared to CMR, while

Table 4. Detection of abnormal LV wall motion (LVWM, in mm) and thickening (LVWT, in %) by gated- CZT SPECT validated versus CMR findings

Sensitivity (%) Spe´cificity (%) Optimal cut-off AUC 95% CI P value

LVWM LAD 96 84 4.8 0.87 0.68–0.97 0.003 CX 66 89 7.9 0.82 0.68–0.96 0.003 RCA 83 100 4.1 0.93 0.86–100 0.001 LVWT LAD 86 84 32 0.83 0.73–0.94 0.01 CX 64 100 27 0.91 0.81–100 0.001 RCA 60 92 28 0.84 0.71–0.96 0.001

Sensitivity and specificity are given for each cut-off value as determined by the receiver operator characteristics area under the curve analysis AUC, area under the curve; LVWM, left ventricular wall motion; LVWT, left ventricular wall thickening; LAD, left anterior descending artery territory; CX, circumflex artery territory; RCA, right coronary artery territory; CZT, myocardial perfusion imaging using ultrafast cadmium-zinc-telluride gamma camera; CMR, cardiac magnetic resonance imaging 1740 Nkoulou et al. Journal of Nuclear CardiologyÒ Myocardial perfusion imaging, CZT detector gamma camera, dobutamine September/October 2019

to detect abnormal contractility with CMR as standard of reference in all coronary territories. The proposed acquisition protocol using the CZT gamma camera offering the opportunity of fast gated acquisitions during subsequent stages of a dobutamine stress may confer and added diagnostic value in eval- uation of multivessel CAD. In fact, MPI is limited to detection of relative perfusion defects, which may underestimate the true extent of myocardial ischemia in coronary territories adjacent to areas with more severe lesions.23 Although extensive coronary calcification may unmask an underlying multivessel disease,28,29 stress- induced wall motion abnormalities would provide direct proof of functionally relevant ischemia such as in stress or stress CMR.30-33 We acknowledge the following limitations: First, although the examination time was similar between our Figure 4. Illustrative case showing contractile dysfunction under increasing doses of dobutamine in a patient with standard protocol and the new proposed protocol proximal occlusion of the left anterior descending artery. The (namely 30 minutes for the entire dobutamine stress perfusion findings denote anterior perfusion defect in the same and 30 minutes for image acquisition including posi- territory. EF, ejection fraction; LD, low-dose dobutamine; HD, tioning the patient, attenuation scan and MPI’s high-dose dobutamine; SAX, short axis view; VLA, vertical acquisition), the new protocol represents increased long axis view; HLA, horizontal long axis view. scanner occupancy time since the CZT camera cannot be used for another acquisition during the full length of LVEF from post-stress SPECT—reflecting daily routine examination. However, this could be avoided by pres- with standard SPECT equipment—showed a modest electing patients with high likelihood of extensive agreement. Despite short acquisition time of 3 min, the coronary calcifications or multivessel disease for this improved count sensitivity enabled by the new CZT specific protocol. Such patients would also justify the camera allowed highly repeatable EF measurements selection of the stress agent dobutamine that is seldom with a variability of only 4%. High repeatability is a used as compared to vasodilator stressing agents in prerequisite for clinical follow-up of individual patients patients unable to provide a significant physiologic and comparison of repeat EF acquired during different stress test. Second, the CMR examination which served hemodynamic conditions or after therapeutic interven- as standard of reference was not performed on the same tions. It is also important in clinical studies to reduce the day, although this may have helped minimizing biolog- sample size in longitudinal studies. The present results ical variability of functional LV parameters. However, it compare well to the variability of 4% reported for EF is questionable whether the biologic response to dobu- from CMR,20-22 and is superior to values from echocar- tamine stress would have been identical in a one-day diography where variability tends to be higher.22-24 protocol, particularly in view of prolonged ventricular One of the major strengths of perfusion SPECT is dysfunction observed after dobutamine stress in patients its established prognostic value based on semi-quanti- with CAD.34 Third, TID as it is described in the tative scoring which has substantially improved literature reflects a combination of true dilation and standardization and significantly reduced observed vari- diffuse subendocardial hypoperfusion at stress. Using ability, not only for assessing perfusion but also for standard gamma camera, this information was gathered evaluating wall motion, global EF and segmental con- during the post-stress period when the heart rate had tractility. By contrast, other modalities such as CMR or returned to baseline and enabled comparison of EDV echocardiography widely rely on an eye ball reading as after similar filling time at stress and rest. Assessing the standardized semi-automated analysis tools are lim- EDV at peak-stress to compute the TID introduces a ited.25 Our results extend the reliability of functional LV reduced filling time owing to increased heart rate and measurements to the latest generation of CZT-equipped that may limitate comparison between TID at peak- gamma camera. Furthermore, this type of scanner stress and post-stress. Fourth, the present article does not enables functional LV assessment during dobutamine explore the diagnostic accuracy of dobutamine CZT as stress allowing evaluation of regional stress-induced compared to dobutamine CMR in the detection of stress- contractile dysfunction.26,27 Using the respective cut-off induced regional contractile dysfunction. This might be from ROC LVWM and LVWT yielded a high accuracy assessed in further studies taking into consideration Journal of Nuclear CardiologyÒ Nkoulou et al. 1741 Volume 26, Number 5;1734–42 Myocardial perfusion imaging, CZT detector gamma camera, dobutamine limitations related to our low temporal resolution (8 bin 4. Sharir T, Berman DS, Lewin HC, et al. Incremental prognostic gated) but also complex modifications of wall motion value of rest-redistribution (201)Tl single-photon emission com- puted tomography. Circulation. 1999;100:1964-70. and thickening within the same territory depending on 5. Sharir T, Germano G, Kang X, et al. Prediction of myocardial the extent of stress-induced perfusion defect and viabil- infarction versus cardiac death by gated myocardial perfusion ity status. Furthermore, our proposed derivated LVWM SPECT: risk stratification by the amount of stress-induced ische- and LVWT regional values have to be validated in mia and the poststress ejection fraction. J Nucl Med. 2001;42:831- different cohorts of patients before integration as diag- 7. 6. Pratali L, Otasevic P, Neskovic A, Molinaro S, Picano E. Prog- nostic reference value. Finally, due to the pilot nature of nostic value of pharmacologic stress echocardiography in patients your study, we did not include a large number of patients with idiopathic dilated cardiomyopathy: a prospective, head-to- with obesity or other features associated with a reduced head comparison between dipyridamole and dobutamine test. J accuracy of SPECT neither did we discuss on the match Card Fail. 2007;13:836-42. between perfusion and contractility. Therefore, our data 7. Quere JP, Monin JL, Levy F, et al. Influence of preoperative left ventricular contractile reserve on postoperative ejection fraction in should be interpreted with caution with regard to low-gradient aortic stenosis. Circulation. 2006;113:1738-44. extrapolation to other patient populations. 8. Gambhir SS, Berman DS, Ziffer J, et al. A novel high-sensitivity rapid-acquisition single-photon cardiac imaging camera. J Nucl Med. 2009;50:635-43. NEW KNOWLEDGE GAINED 9. Herzog BA, Buechel RR, Katz R, et al. Nuclear myocardial per- Due to the fast acquisition with whole heart fusion imaging with a cadmium- zinc-telluride detector technique: optimized protocol for scan time reduction. J Nucl Med. coverage, modern CZT cameras allow left ventricular 2010;51:46-51. volumes and wall motion assessment during peak-stress. 10. Geleijnse ML, Elhendy A, Fioretti PM, Roelandt JR. Dobutamine The distinction of wall motion abnormalities observed at stress myocardial perfusion imaging. J Am Coll Cardiol. peak-stress versus post-stress may offer added informa- 2000;36:2017-27. tion the interaction and time course of ischemia and its 11. Buechel RR, Herzog BA, Husmann L, et al. Ultrafast nuclear myocardial perfusion imaging on a new gamma camera with impact on contractility. semiconductor detector technique: first clinical validation. Eur J Nucl Med Mol Imaging. 2010;37:773-8. 12. Nkoulou R, Pazhenkottil AP, Kuest SM, et al. Semiconductor CONCLUSION detectors allow low-dose-low- dose 1-day SPECT myocardial Real-time ultrafast dobutamine gated-SPECT MPI perfusion imaging. J Nucl Med. 2011;52:1204-9. 13. Bocher M, Blevis IM, Tsukerman L, Shrem Y, Kovalski G, with a CZT device is feasible and provides accurate Volokh L. A fast cardiac gamma camera with dynamic SPECT measurements of peak-stress LV performance. capabilities: design, system validation and future potential. Eur J Nucl Med Mol Imaging. 2010;37:1887-902. 14. Schepis T, Gaemperli O, Koepfli P, et al. Use of coronary calcium Acknowledgements score scans from stand-alone multislice computed tomography for attenuation correction of myocardial perfusion SPECT. Eur J Nucl We would like to thank Ennio Mueller, Edlira Loga, Med Mol Imaging. 2007;34:11-9. Myriam De Bloome, Sabrina Epp, and Patrick von Schulthess 15. Herzog BA, Buechel RR, Husmann L, et al. Validation of CT for their excellent technical support. Philipp A Kaufmann was attenuation correction for high- speed myocardial perfusion supported by a grant from the Swiss National Science imaging using a novel cadmium-zinc-telluride detector technique. Foundation (SNSF). J Nucl Med. 2010;51:1539-44. 16. Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized Disclosures myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from None declared. the Cardiac Imaging Committee of the Council on Clinical Car- diology of the American Heart Association. Circulation. 2002;105:539-42. 17. Bland JM, Altman DG. Statistical methods for assessing agree- References ment between two methods of clinical measurement. Lancet. 1986;1:307-10. 1. Nesto RW, Kowalchuk GJ. The ischemic cascade: temporal 18. Weiss AT, Berman DS, Lew AS, et al. 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